Cholinergic dysfunction is thought to play a significant role in the impairment of explicit memory characteristic of Alzheimer's disease (AD) (1). This observation has provided the rationale for the use of agents that augment cholinergic transmission in this disorder. The goal of this study is to confirm whether treatment with donepezil, a acetylcholinesterase inhibitor, is effective in improving cognition in patients with mild-moderate Alzheimer's disease. Donepezil was recently approved by the FDA. Nevertheless, only one report has appeared (2). The neurologic community has therefore been left with an incomplete knowledge base to prescribe or monitor the drug: unknowns include the expected magnitude of clinical improvement and the incidence and severity of side effects in open clinical settings (as opposed to the subjects carefully selected for clinical trials). An additional benefit is to inform participants in the study whether the benefits of the drug are worth possible side effects and the anticipated expense. Our study is a multicenter, 24 week, double-blind, placebo-controlled crossover study of a single dose of donepezil (5mg) versus placebo in 60 mild to moderate AD patients representative of those encountered in clinical practice. The primary goal of the current study is to assess the effects of donepezil on cognitive function, with an emphasis on explicit verbal memory. Outcome measures of cognition will include the ADAS-COG scale, Verbal fluency test, and NYU stories recall test. In addition, we will examine the rate of decline of the drug's effects during wash-out, a potentially important issue in understanding the longer term effects of cholinergic enhancement.